ABSTRACT Recent estimates indicate that African American and Hispanic older adults have higher rates of Alzheimer?s disease and Alzheimer?s disease related dementias (AD/ADRD). In regards to AD/ADRD disparities by other social statuses, such as gender and socioeconomic status (SES), women and lower SES adults are at higher risk of cognitive decline than their male and high SES counterparts. While previous research has aimed to identify disparities in AD/ADRD, less is known about the underlying mechanisms that shape cognitive functioning trajectories among socially disadvantaged older adults in the US. Therefore, additional research is needed to disentangle the biopsychosocial pathways through which disparities in cognitive impairment may arise across race/ethnicity, gender, and SES groups. One determinant of AD/ADRD that may differentially contribute to cognitive decline, particularly for AA and Hispanic adults, is neighborhood context. Previous literature has documented adverse neighborhood conditions, including lack of cleanliness, safety, and social cohesion, are associated with worse health outcomes. Increased chronic stress among racial/ethnic minorities induced by long-term exposure to social inequality and race-based segregation policies is hypothesized to affect health via allostatic load. Resulting physiological dysregulation characterized by increased systemic inflammation has been associated with increased risk for chronic conditions; however, this mechanism has been less examined in regards to AD/ADRD development. Research examining if stressful neighborhood contexts of older adults are associated with cognitive impairment as well as if inflammatory biomarkers, such as C-reactive protein (CRP), modulate this relationship across racial/ethnic, gender, and socioeconomic groups will contribute to understanding of the biopsychosocial processes underlying AD/ADRD. Additionally, examination of resiliency factors that may be protective against cognitive decline, even among social disadvantaged adults, is needed to more fully understand variability in trajectories of AD/ADRD across groups. Thus, such findings will be important in addressing AD/ADRD disparities. The proposed research will utilize the Health and Retirement Study (HRS) which is a longitudinal, nationally representative dataset of non-Hispanic white, non-Hispanic Black, and Mexican American US older adults to identify how perceived neighborhood conditions (i.e., safety, cleanliness, and social cohesion) are associated cognitive impairment across race/ethnicity, gender, and educational attainment (Aim 1). Moreover, the mediating role of CRP will be examined to further understand if inflammation may be a biological mechanism linking neighborhood-level stress to cognitive impairment development over time (Aim 2). Lastly, the moderating function of resiliency factors (i.e., perceived control, mastery, social support, and healthy behaviors) on the relationship between neighborhood perceptions and cognitive impairment will be assessed (Aim 3). As such, the proposed aims will contribute to increased understanding of the biopsychosocial mechanisms driving disparate rates of AD/ADRD for socially disadvantaged older adults. In order to address each research aim, an interdisciplinary team consisting of scientists trained in biobehavioral health, sociology/demography, and gerontology will be convened. The research team will integrate discipline- specific theoretical perspectives and analytical methodologies to provide a unique approach to identifying the multi-domain processes underlying AD/ADRD development. In particular, the research team will draw from their expertise in biobehavioral processes of aging, social inequality, cognitive functioning, and neighborhoods and health. Each researcher has extensive experience with the HRS and is skilled in advanced statistical analyses, particularly in multi-level and longitudinal methods, which will allow for examination of the complexity of cognitive impairment development across race/ethnicity, gender, and SES. As such, the proposed project is well- positioned to expand upon the dearth of knowledge regarding determinants of AD/ADRD disparities in US adults. Thus, clinical practice and health-related policies will be better able to improve upon current inequalities in AD/ADRD.